Reaction products of 1H-Imidazole-1-ethanol, 4,5-dihydro-, 2-(C7-C17 odd-numbered, C17-unsatd. alkyl) derivs. and sodium hydroxide and chloroacetic acid

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

April 1977

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study meets the EC Standards (conducted equivalent to OECD 401), although prior to GLP principles.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1977

Report date:

1977

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

lack of reported data; no body weight and no necropsy findings

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Group of constituents (alkyl derivatives) in Reaction products of 1H-Imidazole-1-ethanol, 4,5-dihydro-, 2-(C7-C17 odd-numbered, C17-unsatd. alkyl) derivs. and sodium hydroxide and chloroacetic acid

Molecular formula:

For two representative potential structures: C20H36N2O6Na2 : 446 and C18H35N2O4Na: 367

IUPAC Name:

Group of constituents (alkyl derivatives) in Reaction products of 1H-Imidazole-1-ethanol, 4,5-dihydro-, 2-(C7-C17 odd-numbered, C17-unsatd. alkyl) derivs. and sodium hydroxide and chloroacetic acid

Constituent 2

Reference substance name:

Sodium chloride

EC Number:

231-598-3

EC Name:

Sodium chloride

Cas Number:

7647-14-5

Molecular formula:

ClNa

IUPAC Name:

Sodium chloride

Constituent 3

Reference substance name:

Water

EC Number:

231-791-2

EC Name:

Water

Cas Number:

7732-18-5

Molecular formula:

H2O

IUPAC Name:

Oxidane

Test material form:

other: aqueous solution

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: OLAC 1976, Shaws Farm, Blackthorn, Bicester
- Age at study initiation: young adults
- Weight at study initiation: 160-250 g
- Fasting period before study: overnight before dosing
- Housing: in groups of five rats of one sex in polythene breeding cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-21 degrees Celsius
- Humidity (%): 50-70%
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 10/14

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

DOSE VOLUME APPLIED:
Pilot study: 0.85 - 7.6 mL
Main study: 6.0 - 12.0 mL

Doses:

Pilot study: 40, 20, 10 and 5 ml/kg bw
Main study: 60, 42.4 and 30 ml/kg bw

No. of animals per sex per dose:

Pilot study: 1 female and 1 male rat per dose
Main study: 5 female and 5 male rats per dose

Control animals:

other: not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: immediately after dosing, 4 hours after dosing and then daily for 14 days
- Frequency of weighing: only immediately before dosing
- Necropsy of survivors performed: no

Statistics:

The data obtained was subjected to statistical evaluation using the method of Litchfield and Wilcoxon (J. Pharm. Exp. Therap. 1949, 95, 99)

Results and discussion

Preliminary study:

Not applicable

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

42 mL/kg bw

Based on:

test mat.

Remarks:

(aqueous solution)

95% CL:

>= 33 - <= 53

Mortality:

Pilot study:
20, 10 and 5 ml/kg: none of the rats died
40 ml/kg: the female rat dosed at this level died 24 hours after dosing
Main study:
60 ml/kg: one male and 2 female rats died within 4 hours of dosing. The remaining rats died within 24 hours of dosing.
42.4 ml/kg: two female rats died within 24 hours and 1 male rat died within 48 hours.
30 ml/kg: two of the male rats died within 24 hours

Clinical signs:

other: lethargy, hunched stance

Gross pathology:

no data

Other findings:

no data

Any other information on results incl. tables

Dose level; aqueous solution (mL/kg)	No. of rats	Sex (M or F)	Average Bodyweight (g); immediately before dosing	Volume dosed (mL)	Mortality
					0-4 hrs.	1-7 days	8-14 days	Total
40.0	1	M	190	7.6	0	0	0	0	1/2
	1	F	180	7.2	0	1	-	1
20.0	1	M	180	3.6	0	0	0	0	0/2
	1	F	170	3.4	0	0	0	0
10.0	1	M	170	1.7	0	0	0	0	0/2
	1	F	170	1.7	0	0	0	0
5.0	1	M	170	0.85	0	0	0	0	0/2
	1	F	175	0.88	0	0	0	0
60.0	5	M	200	12	1	4	-	5	10/10
	5	F	190	11.4	2	3	-	5
42.4	5	M	220	9.3	0	1	0	1	3/10
	5	F	200	8.5	0	2	0	2
30.0	5	M	250	7.5	0	2	0	2	2/10

Pilot study:

20, 10 and 5 ml/kg: none of the rats died or showed any overt signs of toxicity throughout the 14 -day test period.

40 ml/kg: the female rat dosed at this level became lethargic 4 hours after dosing and died 24 hours after dosing. The male rat was lethargic for 48 hours after dosing, but showed no further overt signs of toxicity

Main study:

60 ml/kg: one male and 2 female rats died within 4 hours of dosing. The remaining rats were lethargic at the 4 hour observation period and died within 24 hours of dosing.

42.4 ml/kg: all the rats became lethargic and adopted a hunched stance within 4 hours of dosing. Two female rats died within 24 hours and 1 male rat died within 48 hours.

30 ml/kg: 3 male rats became lethargic within 24 hours. Two of these 3 rats died 24 hours later.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

LD50 oral (rat): 42 ml/kg (aqueous solution)